Longitudinal diffusion tensor imaging resembles patterns of pathology progression in behavioral variant frontotemporal dementia (BVFTD)
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Objective: Recently, the characteristic longitudinal distribution pattern of the underlying phosphorylated TDP-43 (pTDP-43) pathology in the behavioral variant of frontotemporal dementia (bvFTD) excluding Pick’s disease (PiD) across specific brain regions was described. The aim of the present study was to investigate whether in vivo investigations of bvFTD patients by use of diffusion tensor imaging (DTI) were consistent with these proposed patterns of progression. Methods: Sixty-two bvFTD patients and 47 controls underwent DTI in a multicenter study design. Of these, 49 bvFTD patients and 34 controls had a follow-up scan after approximately 12 months. Cross-sectional and longitudinal alterations were assessed by a two-fold analysis, i.e., voxelwise comparison of fractional anisotropy (FA) maps and a tract of interest-based (TOI) approach, which identifies tract structures that could be assigned to brain regions associated with disease progression. Results: Whole brain-based spatial statistics showed white matter alterations predominantly in the frontal lobes cross-sectionally and longitudinally. The TOIs of bvFTD neuroimaging stages 1 and 2 (uncinate fascicle – bvFTD pattern I; corticostriatal pathway – bvFTD pattern II) showed highly significant differences between bvFTD patients and controls. The corticospinal tract-associated TOI (bvFTD pattern III) did not differ between groups, whereas the differences in the optic radiation (bvFTD pattern IV) reached significance. The findings in the corticospinal tract were due to a ‘dichotomous’ behavior of FA changes there. Conclusion: Longitudinal TOI analysis demonstrated a pattern of white matter pathways alterations consistent with patterns of pTDP-43 pathology.
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Increased CSF NfL, in both genetic and sporadic subtypes, has been associated with various progression measures, including CDR, cognition, behavioral symptoms, frontotemporal grey matter atrophy, white matter tract pathophysiology, GABA-ergic deficit, and survival rates.
“Increased CSF NfL, in both genetic and sporadic subtypes, has been associated with various progression measures, including CDR, cognition (executive functioning; neuropsychiatry unit cognitive assessment tool), behavioral symptoms (FBI), frontotemporal GM atrophy, WM tract pathophysiology, GABA-ergic deficit, and survival rates”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Kassubek et al., 2018
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- Authors
- Kassubek, J., Müller, H.-P., Del Tredici, K., Hornberger, M., Schroeter, M. L., Müller, K., Anderl-Straub, S., Uttner, I., Grossman, M., Braak, H., Hodges, J. R., Piguet, O., Otto, M., & Ludolph, A. C.
- Affiliations
- Universität Ulm (DE)
- University of Cambridge (GB)
- University Hospital Leipzig (DE)
- University of Pennsylvania (US)
- UNSW Sydney (AU)
- ARC Centre of Excellence in Cognition and its Disorders (AU)
- Corresponding author
- Kassubek, Jan
- ORCID
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-03-06
- Volume
- 10
- Pages
- 47-47
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC5845670
- OpenAlex
- W2789454906
- Cited by
- 23
- References
- 52
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 3
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Michael J. Fox Foundation for Parkinson's Research (11362, MJFF-11362)
- Parkinson's Disease Foundation (PDF‐IRG‐1307, FKZ O1GI1007A)
- Deutsche Forschungsgemeinschaft (LU 336/15‐1, project LU 336/15-1)
- Bundesministerium für Bildung und Forschung (FKZ O1GI1007A, O1GI1007A)
- Universität Ulm
- Medical Research Council
- Australian Research Council (CE11000102)
- National Health and Medical Research Council (1103258, 1037746)
- National Institute on Aging (P01AG017586)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- behavioral variant frontotemporal dementia, TDP-43 pathology, fractional anisotropy, white matter changes, corticostriatal pathway, corticospinal tract, optic radiation, disease progression, Pick's disease
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